We examined the occurrence of second primary extracolonic cancers in 1,170 patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1994. Such cancers occurred more often in cases with hereditary nonpolyposis colorectal cancer (HNPCC) than in those without (11.1% vs. 3.6%, P=0.0286). Five HNPCC cases developed 6 cancers in the stomach, endometrium, ovary, and ureter. The mean interval between the first and second operation was 66 months (range: 18-153). These findings thus indicate the importance of targetted surveillance for any second primary cancers in the upper gastrointestinal, female genital, or upper urologic tract, especially in HNPCC patients.